Endocrine System - Physiology


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Endocrine System - Physiology

  1. 1. “The endocrine system” By Dr. Mary A. Youssef ________________________________ Cairo University 2012
  2. 2. Two main control systems 1. The nervous system 2. The endocrine system Slow control system Rapid control system
  3. 3. Endocrine glands Exocrine glands ductless Have ducts Secrete their products (hormones) into the blood Secrete their products to the outer surface or the lumen of GIT Can reach distant tissue Can not
  4. 4. 2. The endocrine system hypothalamus
  5. 5. (Sender) Gland Hormone (signal)  Small amount  Rate of secretion blood  Superadded rhythms  Effector  Opposing effects receptor Target cell Hormone (receiver & transducer)
  6. 6. Classification of hormones 1. According to their chemical nature 1. Protein and polypeptide H. Hypothalamic, pituitary, pancreatic & parathyroid H. 2. Steroid H. Adrenocortical and gonadal H. 3. Hormones derived from a.a. Thyroid h. & adrenal medullary h.
  7. 7. cortex
  8. 8. 2. According to their origin Hypophysiotropic hormones 1. Releasing H.  GHRH  Thyrotropin (TSH) RH (TRH) Hypothalamus  Corticotropin RH  Gonadotropin RH 2. Inhibiting H.  Somatostatin (SS)  Prolactin inhibiting H.
  9. 9. GHRH GHIH (SS) Hypothalamus PIH TRH CRH Anti-diuretic H. (ADH) GnRH Anterior pituitary Growth H. prolactin H. Thyrotropin TSH Corticotropin ACTH posterior pituitary FSH & LH (gonadotropins) gonads T3&T4 Thyroid G. Oxytocin steroids Sex H.
  10. 10. Mechanisms of hormone action What is meant by a target cell? What are the target cells of GHRH? a. cells of the Hypothalamus b. Anterior pituitary cells c. Posterior pituitary cells d. Bone cells GH
  11. 11. I. Mechanism of action of protein & polypeptide hormones:  The hormone (1ry messenger) binds to a cell membrane receptor of target cell  formation of a 2nd messenger inside the cell - cAMP - Calcium-calmodulin - DAG & IP3  changing the activity of certain enzymes
  12. 12. Hormone (1ry messenger) 1. cAMP system Receptor (2ry messenger) Change certain enzymes activity
  13. 13. Hormone (1ry messenger) 2. Calcium-calmodulin system (2ry messenger) calmodulin Change certain enzymes activity
  14. 14. Hormone (1ry messenger) 3. Membrane phospholipid system DAG (2ry messenger) Change certain enzymes activity IP3
  15. 15. II. Mechanism of action of Steroid H. Receptor Increase or a decrease in the synthesis of a certain protein
  16. 16. III. Mechanism of action of Thyroid H. T T T T T T Receptor Increase in the synthesis of certain proteins in almost all cells
  17. 17. Protein or polypeptide H. Hypothalamic, pituitary, parathyroid, pancreatic Cell membrane R. 2ry messenger - cAMP -Ca-calmodulin -DAG & IP3 Change the activity of already present enzymes Steroid H. H. derived from a.a. Adrenocortical & Gonadal h. Thyroid & adrenal medullary h. Cytoplasmic R. Nuclear R. _ _ Synthesis of new proteins Synthesis of new proteins
  18. 18. Regulation of hormone secretion Hypothalamus Ant. Pituitary G. Hormone -hormone feedback Target gland Substratehormone feedback Target gland hormone Substrate Mineral Mineralhormone feedback
  19. 19. The pituitary gland (hypophysis)
  20. 20. GHRH GHIH (ss) PIH TRH CRH GnRH Hypothalamohypophyseal portal vessels Adenohypophysis
  21. 21. Hypothalamic neurons Hypothalamohypophyseal tract
  22. 22. Hypothalamus Anterior pituitary gland hormones Anterior pituitary gland hormones  The anterior pituitary produces & secretes its own hormones Anti-diuretic H  Its Hormones are given the extension; (ADH) tropic, tropin or trophic posterior Anterior pituitary  It is the master pituitary for the majority of the Oxytocin endocrine glands Growth H. prolactin H. Thyrotropin TSH Corticotropin ACTH FSH & LH (gonadotropins) gonads T3&T4 Thyroid G. steroids Sex H.
  23. 23. Which of these is not produced by the anterior pituitary? ► ACTH ► follicle-stimulating ► Somatostatin (ss) ► Somatotropic H. hormone (FSH)
  24. 24. Growth hormone (somatotropic hormone) It is a protein hormone that stimulates growth Actions of growth hormone 1. On bone growth somatomedin GH
  25. 25. 2. On protein metabolism It is an anabolic hormone mRNA 1. Rate of DNA transcription 2. a.a. transport into the cell a.a. a.a .
  26. 26. 3. On carbohydrate metabolism It increases blood glucose level (diabetogenic action) Glycogen glucose 1 Insulin R. X Glycogen synthase Glucose 6-PO4 2 Glucose transporter phosphorylase Glycolysis pyruvate
  27. 27. 4. On lipid metabolism GH Lipolysis Fat (T.G.) FA Glycerol FFA
  28. 28. Factors affecting GH secretion GH secretion is increased by GHRH  Low blood glucose and FFA  Protein meal  Emotional stress  Deep sleep GH secretion is Decreased by somatostatin  High blood glucose and FFA  treatment with corticosteroids
  29. 29. Disorders of GH secretion A. Growth hormone deficiency (dwarfism)  Decrease in the size of the trunk & extremities  Normal mental & sexual development
  30. 30. Pituitary infantilism Failure of:  Physical development  Sexual development GH Gonadotropins
  31. 31. B. Growth hormone Excess  Before closure of epiphyses Gigantism taller than normal  After closure of epiphysis Acromegaly
  32. 32. Main features of acromegaly No linear growth of bones 1. Bones of hands and feet 2. Bones of the face 3. Mandible 4. The spine 5. Diabetes
  33. 33. Hormone Actions Deficiency Pituitary On bone dwarfism: linear growth (via Only failure somatomedin) of physical develop. Growth  On protein H. Anabolic (Ant. Pituitary  On CHO Pituitary( infantilism: Diabetogenic Failure of  On lipid physical & lipolysis sexual develop. Excess  Gigantism: Before closure of epiphysis Acromegaly After closure of epiphysis
  34. 34. Growth hormone A. directly stimulates growth of cartilage and bone. B. enhances protein breakdown in nonvital muscles. C. levels are subnormal in Gigantism. D. promotes lipolysis in adipose tissue.
  35. 35. Posterior pituitary gland hormones
  36. 36. Antidiuretic hormone (ADH) (Vasopressin)  It is a protein hormone  Formed in supraoptic n. of the hypothalamus and secreted from the posterior pituitary
  37. 37. Actions of ADH (vasopressin) 1. On Kidney Anti-diuresis (retention of water)
  38. 38. 2. On blood vessels Pressor effect 3. On smooth muscles Contraction of the smooth muscles
  39. 39. Summary of the actions of ADH Antidiuretic H.
  40. 40. Antidiuretic hormone Blood volume Vascular resistance Arterial blood pressure
  41. 41. Regulation of ADH secretion H2 o + ADH- secretion is increased by Hypovolaemia  osmotic pressure of ECF Baroreceptors & low pressure volume (e.g. Hge)  blood R  Stress  Drugs (e.g. morphine & nicotine) Na+ osmoreceptors
  42. 42. Disorders of ADH secretion ADH deficiency 1. Polyuria 2. Polydipsia 3. Loss of water soluble vitamins Diabetes insipidus
  43. 43. Oxytocin  It is a protein hormone  Formed in paraventricular n. of the hypothalamus and secreted from the posterior pituitary Actions of Oxytocin 1. Uterine contraction during delivery 2. Milk ejection action during suckling 3. Mild antidiuretic action
  44. 44. The Thyroid gland
  45. 45. Histology 1. Follicles Lined with a single layer of epithelial cells Its centre is filled with colloid 2. Parafollicular cells
  46. 46. Hormones secreted from the thyroid gland From thyroid follicle cells From parafollicular cells Thyroid Hormones  T3 (tri-iodothyronine)  T4 (tetra-iodothyronine, thyroxine) Thyrocalcitonin (calcitonin) It affects body metabolism It affects Ca homeostasis
  47. 47. Actions of Thyroid hormones T T T T T T Receptor Synthesis of new protein
  48. 48. mRNA Physical mental Proteins for growth & maturation Sexual 5 Respiration 6 CVS 7 CNS O2 Enzymes & transport ptns O2 consumption No of mitochondria Metabolic rate 2 substrate 3 GIT 4 Metabolism blood glucose blood FFA (lipolysis) 1 Calorigenic effect
  49. 49. Hypothalamus Cold & + emotional stress Regulation of thyroid hormones ++ Thyroid h. secretion is Ant. regulated by : -1. TRH pituitary -- 2. TSH 3. Feedback Mechanism ++ 4. Cold 5. Stress Iodine deficiency Thyroid
  50. 50. Disorders of thyroid hormone secretion A. Hypothyroidism In adults Myxoedema 1. BMR & calorigenesis 2. Generalized decrease in activity of all body systems 3. Myxoedematous tissue CVS: Heart rate & Cardiac output GIT: intestinal motility (constipation) CNS: slow mentation & sluggish reactions, S
  51. 51. Since birth Cretinism Delayed physically: Dwarf, teeth erupt later than normal Delayed mentally Delayed sexually Special features:  Depressed nasal bridge  Wide nostrils  Protruding tongue  Protuberant abdomen
  52. 52. B. Hyperthyroidism (thyrotoxicosis) One of its types is Grave’s disease (exophthalmic goitre) Autoimmune disease TSH-R(stim) Ab TSH-R (stim) Ab
  53. 53. Characters of hyperthyroidism 1. BMR & calorigenesis 2. Generalized increase in activity of all body systems 3. Loss of weight in spite of increased food intake CVS: Heart rate & Cardiac output GIT: intestinal motility (diarrhea) CNS: tremors, irritability, insomnia
  54. 54. Calcium homeostasis  The adult human body contains 1 Kg of calcium  Functions of calcium: 1. Mineralization of bones & teeth 2. Blood clotting 3. Neuromuscular excitability 4. Muscle contraction & relaxation 5. Release of neurotransmitters 6. Hormonal secretion & act as a 2ry messenger
  55. 55. Diet 1g 175 mg 8 Extracellular fluid 1g 10 g filtered/day 1 Kg 175 mg 99% stable in 1% exchangable mineralized bone in bone fluid
  56. 56. Plasma calcium: Its concentration is about 10mg/dl 1. Ionized 50% 2. Bound to protein 40% 3. Complex & diffusible form 10% Solubility product: [Ca2+] x [PO43-] = constant
  57. 57. Bone Bone tissue is formed of: 1. Organic matrix (formed mainly of collagen) 2. Crystalline salts (mainly hydroxyapatite crystals & calcium phosphate) 3. Bone cells A. Osteoblast Ca hydroxide Ca phosphate B. Osteocyte C. Osteoclasts hydroxyapatite
  58. 58. Secrete  Bone matrix proteins  Alkaline phosphatase Phosphate ester phosphate Secrete Bone forming cells Ca phosphate  H+ that dissolve Bone hydroxyapatite eating Acid protease cells that dissolve collagen
  59. 59. Osteoblasts 10 mg/dl Hydroxy -apatite crystals Osteocytes Bone fluids  Ca++  Ca bound to ptn  Complex form Outer surface of the bone
  60. 60. Hormonal control of plasma Ca level Ca++ 3 hormones play a role in the control of plasma Ca Ca++ level 1. Parathormone hormone (PTH) Source: Parathyroid gland Hydroxyapatite Actions: crystals Ca++ 1. On bones A.Rapid phase 2. On kidney B.Slow Phase 3. On GIT Ca++ Ca++ Ca++ PTH
  61. 61. 2. On kidney DCT PCT Ca++ + - PO4
  62. 62. Ca++ reabsorption Phosphate reabsorption ECF Ca++ ECF PO43- Ca++ absorption
  63. 63. 2. Vitamin D3 Source: Skin 25-hydroxycholecalcife rol 1, 25-dihydroxy cholecalciferol ECF Ca++ ECF PO43-
  64. 64. 3. Calcitonin Source: parafollicular cells Actions: 1. On Bone (inhibits activity of osteoclats) 2. On kidney Ca++ - ECF Ca++ ECF PO43- PO4
  65. 65. Tetany It is a state of increased neuromuscular excitability due to decreased ionized calcium Causes Hypoparathyroidism Vitamin D deficiency Renal disease Akalemia Types:  Latent tetany: when the total plasma Ca is between 9 and 7 mg/dl. Its manifestations do not appear during rest  Manifest tetany: when the total plasma Ca drops below 7mg%. The patient is presented by spasmodic contractions
  66. 66. The adrenal glands Each adrenal gland consists of two endocrine organs 1. Adrenal cortex Secretes steroid hormones 2. Adrenal medulla Secretes catecholamines cortex
  67. 67. Cortex Medulla Zona glomerulosa Mineralocorticoids Aldosterone Glucocorticoids Zona Fasciculata Zona Reticularis cortisol Sex Hormones Androgens & estrogen
  68. 68. A. Glucocorticoids Cortisol = 95% of total glucocorticoid activity.
  69. 69. Actions of cortisol depends on its plasma level: 1. Permissive Actions its presence even at small amounts permits certain processes to occur 2. Physiological Actions Effects of the normally present hormone levels in plasma 3. Pharmacological Actions Effects of the high levels of hormone in plasma
  70. 70. 1. Permissive Actions It means that cortisol does not initiate the changes, but its presence even at small amounts permits certain processes Glycogenolysis Glucagon & catecholamines Arteriolar V.C. response & bronchodilatation Catecholamines
  71. 71. 2. physiological Actions I. Effect on metabolism 1 Gluconeogenesis a.a. Glucose glycogen Blood glucose Blood FFA Glycogen protein glucose 2 Glycogen phosphorylase Lipolysis synthase Glucose 6-PO4 Fat (T.G.) 3 Glycolysis FA Glycerol pyruvate
  72. 72. I. Effect on metabolism II. Effect on CNS Required for normal EEG pattern III. Weak mineralocorticoid effect IV. Anti-stress effect Permissive action catecholamines V.C. Blood glucose Plasma a.a. Plasma FFA
  73. 73. 3. pharmacological Actions I. Anti-allergic effect II. Anti-inflammatory effect Mast cell
  74. 74. Phospholipids PGs 1 V.D.  Capillary permeability  Local redness Local heat Local swelling Lysosomes 2  White blood cells Destruction of Local pain Eosinophils 3 cells Loss of function Basophils Phagocytic cells 4  Fibroblasts 5 Walling off of infections
  75. 75. 5 4 Control of glucocorticoid secretion hypothalamus 1 3 2
  76. 76. H2O Na+ Aldosterone actions B. Mineralocorticoids K+ Actions: DCT Collecting duct ECFV
  77. 77. Disorders of adrenocortical hormones 1.cause: Cushing’s syndrome Hypersecretion of cortisol + excess androgen 2. Features I. Excess cortisol 1. CHO metabolism (DM) 2. Excess protein catabolism 3. Disturbed fat deposition II. Mineralocorticoid effect III. Excess Androgens  Moon face  Buffalo hump  Purple striae
  78. 78. Addison’s syndrome 1.cause: Hyposecretion of adrenocortical hormones 2. Features I. Mineralocorticoid deficiency 1. Hypotension 2. Polyuria & polydipsia 3. Hyperkalemia Aldosterone H2O actions Na+ B. K Actions Mineraloco : rticoids ECFV +
  79. 79. II. Glucocorticoid deficiency 1. Metabolism Depression of many metabolic functions - CHO metabolism 2. Appetite 3. During stress 4. ACTH hypoglycemia Loss of appetite weight loss Decreased resistance to stress ACTH skin pigmentation
  80. 80. Control of glucocorticoid secretion hypothalamus
  81. 81. 1 The Pancreas
  82. 82. Actions of insulin I. On CHO metabolism: In skeletal m., cardiac m. & adipose tissue Glycogen Glycogen synthase glucose phosphorylase Glucose 6-PO4 Glycolysis Insulin R. Glucose transporter pyruvate
  83. 83. In the liver Glucose Glucose 1. Indirectly facilitates glucose entery 2. Promotes glycogenesis 3. Inhibits glycogenolysis 4. Inhibits gluconeogensis + + Glycogenesis Glucose 6 P Glycogen - Glycogenolysis - gluconeogensis
  84. 84. II. On lipid metabolism: lipogenesis III. On protein metabolism: (Anabolic) IV. On Growth mRNA 1. Rate of DNA transcription 2. a.a. transport into the cell a.a. a.a .
  85. 85. Actions of Glucagon Insulin Glucagon On CHO metabolism glycogenolysis gluconeogenesis glycogenolysis gluconeogenesis On lipid metabolism Lipogenesis Lipolysis On protein metabolism Anabolic Catabolic hyperglycemia hypoglycemia Stimulus
  86. 86. Diabetes mellitus Organ/tissue Response Blood urine Signs & symptoms Decreased glucose uptake Hyperg glucos Polyuria lycemia uria dehydration Glycogenolysis Gluconeogenesis Hyperg Osmotic lycemia diuresis Protein catabolism Polydipsia Weight loss Polyphagia (Hyperphagia)
  87. 87. Glucose Homeostasis The importance to maintain a normal blood glucose concentration Insulin returns blood glucose Body response to ingestion of a meal (high 140 level back to control level glucose) 120 100 1h 2h 3h 4h
  88. 88. Mechanisms controlling blood glucose concentration 1. Glucostatic function of the liver  Glycogenesis (after meals)  Glycogenolysis (between meals)  Gluconeogenesis (during fasting) 2. Hormonal Mechanism Both insulin & glucagon function as important feedback control systems to maintain a normal blood glucose level
  89. 89. Thank You